New-onset symptomatic seizures in adults can be related to many conditions including metabolic unbalances and can be the first clinical manifestation of non-ketotic hyperosmolar hyperglycaemia (NKHH). We analysed electroclinical and MRI data of three patients with NKHH-related focal seizures and those reported in the literature searching for peculiar signal abnormalities and the possible association between their brain location and the putative seizure onset zone (pSOZ).

In all our patients the brain MRI (1.5T) showed T2- and T2*-hypointensity of the subcortical white matter in locations consistent with the pSOZ identified by electroclinical data. Diffusion restriction and cortical/leptomeningeal contrast enhancement were also noticed in two patients.

From literature review we found that subcortical T2-hypointensity is the most frequent radiological abnormality (84% of cases). The concordance between brain location of imaging abnormalities and pSOZ was identified 76% of cases.

In patients with NKHH, seizures are fostered by depolarisation of the resting membrane potential and/or the reduced seizure threshold due to hyperglycaemia. The subcortical T2-T2* hypointensity could be the radiological manifestation of an intermediate step leading to seizure: the osmotic gradient between intra- and extra-vascular compartment induced by hyperglycaemia causes glial cells dehydration (and, then, T2-T2* hypointensity) and Na+/K+ ATPase dysfunction with seizure facilitation.

The subcortical T2/T2* hypointensity is the most reliable radiological abnormality in adult patients with new-onset seizures and decompensated diabetes mellitus, and its brain location is often consistent with pSOZ. This information facilitates the etiological diagnosis of NKHH-related seizure, allowing for the timely treatment of hyperglycaemia and, often, a favourable prognosis.